This invention pertains to a process for the preparation of known therapeutic agents and to chemical intermediates useful therein.
Compounds of the formula: ##STR1## in which Z.sup.2 is hydrogen, methyl, or ethyl are broad spectrum antineoplastic agents, see published PCT Application WO 86/05181 and corresponding U.S. Pat. No. 4,684,653. N-(4-[2-(2-amino-4-hydroxy-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-6-yl)e thyl]benzoyl)-L-glutamic acid, which is representative, has been prepared previously through an eighteen step synthesis in which a 2-(protected amino)-4-hydroxy-6-[2-(4-carboxyphenyl)ethenyl]pyrido[2,3-d]pyrimidine is coupled with a diester of L-glutamic acid utilizing peptide condensation techniques. The resultant dialkyl N-(4-[2-(2-protected amino-4-hydroxypyrido[2,3-d]pyrimidin-6-yl)ethenyl]benzoyl)-L-glutamate is then hydrogenated, following which the protecting groups are removed [see Taylor et al., J. Med. Chem. 28: 7, 914 (1985)].